The present invention provides a process for the preparation of 4-aryl piperidines of general formula (I). 
The present invention also provides intermediates useful in the disclosed process.
The compounds of formula I are intermediates useful for the preparation of the 4-aryl piperidine compounds of the general formula II, wherein X is aryl and Y is hydrogen or fluoride. 
The compounds of formula II, along with their use as melanocortin receptor agonists, were disclosed in WO 02/068388, (published on Sep. 6, 2002). The compounds of formula II are also useful as agents for the treatment, control or prevention of diseases, disorders or conditions responsive to the activation of one or more of the melanocortin receptors including, but are not limited to, MC-1, MC-2, MC-3, MC-4, or MC-5. Such diseases, disorders or conditions include, but are not limited to, obesity, diabetes mellitus, hypertension, hyperlipidemia, osteoarthritis, cancer, gall bladder disease, sleep apnea, depression, anxiety, compulsion, neuroses, insomnia/sleep disorder, substance abuse, pain, male and female sexual dysfunction, fever, inflammation, immunemodulation, rheumatoid arthritis, skin tanning, acne and other skin disorders, neuroprotective and cognitive and memory enhancement including the treatment of Alzheimer's disease. Some compounds encompassed by formula I show highly selective affinity for the melanocortin-4 receptor (MC-4R) relative to MC-1R, MC-2R, MC-3R, and MC-5R, which makes them especially useful in the prevention and treatment of obesity, as well as male and/or female sexual dysfunction, including erectile dysfunction.
WO 02/068388, (published on Sep. 6, 2002) describes processes for preparing the compounds of formula II. However, a large number of synthetic transformations are required (the longest linear sequence being about 13 steps) with an overall yield of less than 10%. Additionally, explosive reagents, such as zinc azide were required.
With the present invention, there is produced more efficiently the compound of structural formula I in considerably fewer chemical steps utilizing fewer and less expensive chemical reagents. The longest linear synthetic sequence comprises 4 steps with a higher overall yield.
The preparation and coupling of acyl pyridinium ions is described in Comins, D. L., J. Org. Chem., vol. 47, pp. 4315–4319 (1982). The preparation and reduction of dihydropyridine rings is described in European Patent Application No. 831087 (1998).